Dopamine, psychosis and schizophrenia: the widening gap between basic and clinical neuroscience

Kesby, J P, Eyles, D W, McGrath, J J and Scott, J G (2018) Dopamine, psychosis and schizophrenia: the widening gap between basic and clinical neuroscience. Translational psychiatry, 8 1: 30. doi:10.1038/s41398-017-0071-9


Author Kesby, J P
Eyles, D W
McGrath, J J
Scott, J G
Title Dopamine, psychosis and schizophrenia: the widening gap between basic and clinical neuroscience
Journal name Translational psychiatry   Check publisher's open access policy
ISSN 2158-3188
Publication date 2018-01-31
Year available 2018
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1038/s41398-017-0071-9
Open Access Status DOI
Volume 8
Issue 1
Start page 30
Total pages 12
Place of publication NEW YORK
Publisher NATURE PUBLISHING GROUP
Language eng
Abstract The stagnation in drug development for schizophrenia highlights the need for better translation between basic and clinical research. Understanding the neurobiology of schizophrenia presents substantial challenges but a key feature continues to be the involvement of subcortical dopaminergic dysfunction in those with psychotic symptoms. Our contemporary knowledge regarding dopamine dysfunction has clarified where and when dopaminergic alterations may present in schizophrenia. For example, clinical studies have shown patients with schizophrenia show increased presynaptic dopamine function in the associative striatum, rather than the limbic striatum as previously presumed. Furthermore, subjects deemed at high risk of developing schizophrenia show similar presynaptic dopamine abnormalities in the associative striatum. Thus, our view of subcortical dopamine function in schizophrenia continues to evolve as we accommodate this newly acquired information. However, basic research in animal models has been slow to incorporate these clinical findings. For example, psychostimulant-induced locomotion, the commonly utilised phenotype for positive symptoms in rodents, is heavily associated with dopaminergic activation in the limbic striatum. This anatomical misalignment has brought into question how we assess positive symptoms in animal models and represents an opportunity for improved translation between basic and clinical research. The current review focuses on the role of subcortical dopamine dysfunction in psychosis and schizophrenia. We present and discuss alternative phenotypes that may provide a more translational approach to assess the neurobiology of positive symptoms in schizophrenia. Incorporation of recent clinical findings is essential if we are to develop meaningful translational animal models.
Keyword Ultra-High Risk
Increased Synaptic Dopamine
Nucleus-Accumbens-Septi
Spatial Working-Memory
Basal Ganglia
Dorsomedial Striatum
Prefrontal Cortex
D-Amphetamine
Methylazoxymethanol Acetate
Prepulse Inhibition
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID APP1105807
APP1056929
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collection: Pubmed Import
 
Versions
Version Filter Type
Citation counts: Google Scholar Search Google Scholar
Created: Wed, 07 Feb 2018, 11:07:04 EST